Recombinant Human Antithrombin (ATryn®) in the Treatment of Patients With DIC Associated With Severe Sepsis

Exploratory Efficacy and Safety, Pharmacokinetics and Dose Finding Study of ATryn® (Antithrombin Alfa) in Patients With Disseminated Intravascular Coagulation Associated With Severe Sepsis

The primary objective of the study is to explore the efficacy and safety of ATryn® (antithrombin alfa) for the treatment of disseminated intravascular coagulation (DIC) associated with severe sepsis, when administered by continuous intravenous (IV) infusion over five days.

Study Overview

• Status: Terminated
• Conditions: Disseminated Intravascular Coagulation
• Intervention / Treatment: Drug: Antithrombin alfa (INN name); Drug: Control (Standard treatment)

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent has been obtained from the patient or his/her legally acceptable representative
• Severe sepsis
• Disseminated intravascular coagulation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AT-150; Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175%	Drug: Antithrombin alfa (INN name)
Experimental: AT-250; Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275%	Drug: Antithrombin alfa (INN name)
Active Comparator: Control; The best standard treatment for the underlying condition only	Drug: Control (Standard treatment)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients Alive on Day 28, Having Had an Improvement in the DIC Score (Overt or Non-overt) by at Least 2 Points Between Baseline and Day 6 and Having Had no Worsening of the SOFA Score Between Baseline and Day 6.	Disseminated Intravascular Coagulation (DIC) ranges from 0 to 8 points, the higher the score the worse coagulation/outcome. Sepsis-related Organ Failure Assessment (SOFA) is a composite score of scores for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 to 4 with a higher score given for worse organ function. The scores are then added together to give a total range from 0 to 24 with a higher score representing a worse outcome.	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality at Day 28		Day 28
Mortality at Day 90		Day 90
Change From Baseline to Day 6 in SOFA Score Among Survivors on Day 6	Sepsis-related Organ Failure Assessment (SOFA) is a composite score of scores for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 to 4 with a higher score given for worse organ function. The scores are then added together to give a total range from 0 to 24 with a higher score representing a worse outcome.	Baseline to Day 6
Change From Baseline to Day 6 in DIC Score Among Survivors on Day 6	Disseminated Intravascular Coagulation (DIC) ranges from 0 to 8 points, the higher the score the worse coagulation/outcome	Baseline to Day 6
Days Alive and Out of ICU Day 28	Days alive and out of ICU at day 28 for all patients	Baseline to Day 28
Days Alive and Out of Hospital Day 28	Days alive and out of Hospital at day 28 for all patients	Baseline to Day 28
Days Alive and Free of Inotrope/Vasopressor Support Day 28	Days alive and free of inotrope/vasopressor at day 28 for all patients	Baseline to Day 28
Days Alive and Off Ventilator Day 28	Days alive and free of mechanical ventilation at day 28 for all patients	Baseline to Day 28
Days Alive and Free of Need for Renal Replacement Therapy Day 28	Days alive and out of renal replacement therapy at day 28 for all patients	Baseline to Day 28
Change From Baseline to Day 6 in Inflammation Marker IL-6		Baseline to Day 6
Change From Baseline to Day 6 in Inflammation Marker Procalcitonin		Baseline to Day 6

Collaborators and Investigators

• Sponsor: LEO Pharma

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: July 23, 2007
• First Submitted That Met QC Criteria: July 23, 2007
• First Posted (Estimated): July 25, 2007

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 21, 2025
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: DIC associated with severe sepsis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Thrombophilia; Sepsis; Disseminated Intravascular Coagulation; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Anticoagulants; Serine Proteinase Inhibitors; Antithrombins; Antithrombin III
• Other Study ID Numbers: LEO 90010-I21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO